LDLs are formed from IDLs due to the catalytic activity of hepatic lipase. This enzyme is bound to hepatocytes in an inactive form. HL is detached by HDLs and transferred to triglyceride-rich lipoproteins where it actively hydrolyze triglyceride and shrinks the lipoprotein. 'Reverse cholesterol transport' is when HDLs return cholesterol to the liver.
Low density lipoproteins (LDLs) are formed from intermediate density lipoproteins (IDLs) shown in the top center of the diagram. This conversion is due to the catalytic activity of hepatic lipase (HL, red) inscribed on the arrow. This enzyme hydrolyzes any triglyceride in the IDL and also removes excess phospholipids from the IDL coat as it shrinks. (Note relative sizes of the IDL and LDL).
Hepatic lipase resides on HSPGs (not shown) on hepatocyte membranes and is inactive. It must be dislodged from the HSPGs, transported into circulation and activated at the appropriate time. The catalytic activities of hepatic lipase would destroy cell membranes if it circulated in an active form. However, it is readily accessible, though inactive, while bound to hepatocytes (HL on curved line (hepatocyte) at upper left ).
Hepatic lipase is most effectively dislodged by the larger types of HDL (HDL2) This is shown by the HDL2 from the lower left contacting the hepatic lipase (HL) attached to the hepatocyte (upper left). From there HDL leaves, with the HL attached, to re-enter the general circulation. The HL is still inactive.
Hepatic lipase can be transferred to other lipoproteins under the right conditions. It does not circulate freely in the plasma. There are several possible explanations as to what causes this transfer. One possibility is the increase of plasma free fatty acids after a meal.
When hepatic lipase is transferred to the recipient lipoprotein it becomes active hydrolyzing triglyceride and reducing the phospholipid in the coat. The lipoprotein decreases in size and becomes triglyceride-poor -- and therefore cholesterol ester-rich. The diagram represents these events showing an IDL with a core half triglyceride (lavender) and half phospholipid (orange)being converted to a smaller cholesterol ester-rich low density lipoprotein (LDL).
Low density lipoprotein is small enough to penetrate capillary walls and deliver cholesterol esters to those cells displaying low density lipoprotein receptors (LDL-R). This receptor binds to apoprotein B100 on the particles resulting in phagocytosis.
The liver displays abundant LDL-R receptors and accounts for most LDL uptake. Body cells that produce steroids also have a constant need for cholesterol as shown in the upper right of the diagram.
Unfortunately, low density lipoproteins also enter inflamed areas of arteries. There macrophages secrete numerous chemicals involved in the inflammatory response and the LDLs become oxidized. Scavenger receptor A (SR-A), abundant on active macrophages, specifically binds with oxidized LDLs (oxLDL) and phagocytize them. This increase in cholesterol within macrophages converts them to foam cells. The foamy appearance is due to the accumulation of lipid droplets in their cytoplasm (lower right).
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